急性高原反应,高原肺水肿患者支气管肺泡灌洗液的研究

为了探讨急性高原病的发病机理，本文观察了急性高原反应、高原肺水肿及同海拔健康者各10名支气管肺泡灌洗液的改变，发现肺水肿患者肺泡灌洗液中含有大量的蛋白质，红细胞及白细胞，同时也含有大量的免疫球蛋白（IgC、IgA、IgM）和补体C3、C4；而急性高原反应患者肺泡灌洗液改变同高原健康人相比无异常发现，提示高原肺水肿患者肺循环有“漏孔”存在，高原肺水肿是一种高渗性肺水肿。而急性高原反应发病中未有肺泡腔渗漏发现。     

血管外肺水监测的研究进展

血管外肺水（EVLW）即肺血管外的液体,由细胞内液、肺间质内液和肺泡内液组成,通常情况下细胞内液变化较小,而肺间质内液和肺泡内液却能准确反映肺水肿的严重程度,因此,EVLW的变化与肺水肿密切相关.正常值为3.0-7.0 mL/kg,大于3.0-7.0 mL/kg提示有肺水肿.超过正常2倍的EVLW就会影响气体弥散和肺的功能,出现肺水肿的症状和体征.     

p38丝裂原活化蛋白激酶抑制剂对大鼠急性肺损伤血清及支气管肺泡灌洗液中细胞因子的影响

目的 探讨p38丝裂原活化蛋白激酶(MAPK)抑制剂治疗内毒素型急性肺损伤(ALI)的机制.方法 腹腔内注射 气管内给内毒素复制大鼠ALI模型.用酶联免疫吸附试验测定血清及肺泡灌洗液中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)及IL-10水平.结果 大鼠血清和支气管肺泡灌洗液中TNF-α、IL-6含量,实验组和预处理组显著高于对照组(P＜0.01),实验组高于预处理组(P＜0.05);血清和支气管肺泡灌洗液中IL-10含量,实验组和预处理组高于对照组(P＜0.01),而实验组和预处理组之间无显著性差异.结论 TNF-α、IL-6和IL-10在大鼠内毒素ALI过程中可能起重要作用.p38MAPK抑制剂可能通过抑制TNF-α、IL-6过度分泌而减轻肺损伤.     

Nrf2在丙泊酚抑制内毒素性急性肺损伤中的作用

目的 观察丙泊酚对内毒素诱发的急性肺损伤的保护作用及与肺上皮细胞核内Nrf2表达的关系.方法 腹腔注射内毒素建立小鼠急性肺损伤模型,实验动物分为对照组、内毒素组、内毒素+丙泊酚组、内毒素+脂肪乳剂组和丙泊酚组,分别检测小鼠生存率、肺湿重/干重比、支气管肺泡灌洗液蛋白浓度和白细胞计数、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量、肺上皮细胞核内Nrf2水平.结果 腹腔注射内毒素导致小鼠生存率降低,肺湿重/干重比、支气管肺泡灌洗液蛋白浓度和白细胞计数增加,SOD活性降低和MDA含量增加,丙泊酚能明显提高小鼠肺上皮细胞核内Nrf2表达.结论 丙泊酚对内毒素诱发的急性肺损伤具有保护作用,这可能与丙泊酚激活肺上皮细胞核内Nrf2表达有关.     

乌司他丁对大鼠重症急性胰腺炎肺损伤中SP-A的影响研究

【摘要】目的 观察乌司他丁对重症急性胰腺炎（SAP）肺损伤大鼠的肺泡表面活性物质相关蛋白A（SP-A）含量的影响,探讨其对SAP肺脏损伤的保护机制。方法 SD大鼠60只,随机分为空白对照组、SAP模型组、乌司他丁组 3组,每组20只。通过胆胰管内逆行注入5%牛磺胆酸钠法建立大鼠SAP 致急性肺损伤模型,用ELISA法检测支气管肺泡灌洗液(BALF)中SP-A的含量,离心灌洗液行细胞分类计数,测量肺湿/干重比以判断肺水肿情况。结果 SAP组大鼠肺湿/干重比值、支气管肺泡灌洗液中的中性粒细胞含量高于空白对照组和乌司他丁治疗组,乌司他丁组大鼠肺湿/干重比值和中性粒细胞含量高于空白对照组(P < 0.05）;SAP组支气管肺泡灌洗液中SP-A含量和巨噬细胞低于空白对照组和乌司他丁组,乌司他丁组低于对照组,SAP组和乌司他丁组淋巴细胞高于空白对照组(P < 0.05);3组大鼠肺泡灌洗液中总细胞数差异无统计学意义。结论 SAP肺损伤时肺泡内SP-A含量明显减少,乌司他丁对SAP时肺泡内SP-A起保护作用。     

中介素在低氧性肺动脉高压大鼠中的变化和意义

目的 观察比较中介素在低氧性肺动脉高压大鼠血浆和支气管肺泡灌洗液含量的变化.方法 雄性Wistar大鼠被随机分为4组,对照组、低氧1周组、2周组、3周组.利用放免分析法测定大鼠血浆和支气管肺泡灌洗液的含量.结果 低氧组大鼠血浆和支气管肺泡灌洗液中介素含量明显高于对照组.同时支气管肺泡灌洗液和血浆的变化趋势一致.结论 中介素血浆和支气管肺泡灌洗液含量增高,提示机体可能对缺氧性肺动脉高压起到一定的缓冲和保护作用.     

中介素在低氧性肺动脉高压大鼠中的变化和意义

目的 观察比较中介素在低氧性肺动脉高压大鼠血浆和支气管肺泡灌洗液含量的变化.方法 雄性Wistar大鼠被随机分为4组,对照组、低氧1周组、2周组、3周组.利用放免分析法测定大鼠血浆和支气管肺泡灌洗液的含量.结果 低氧组大鼠血浆和支气管肺泡灌洗液中介素含量明显高于对照组.同时支气管肺泡灌洗液和血浆的变化趋势一致.结论 中介素血浆和支气管肺泡灌洗液含量增高,提示机体可能对缺氧性肺动脉高压起到一定的缓冲和保护作用.     

中介素在低氧性肺动脉高压大鼠中的变化和意义

目的 观察比较中介素在低氧性肺动脉高压大鼠血浆和支气管肺泡灌洗液含量的变化.方法 雄性Wistar大鼠被随机分为4组,对照组、低氧1周组、2周组、3周组.利用放免分析法测定大鼠血浆和支气管肺泡灌洗液的含量.结果 低氧组大鼠血浆和支气管肺泡灌洗液中介素含量明显高于对照组.同时支气管肺泡灌洗液和血浆的变化趋势一致.结论 中介素血浆和支气管肺泡灌洗液含量增高,提示机体可能对缺氧性肺动脉高压起到一定的缓冲和保护作用.     

中介素在低氧性肺动脉高压大鼠中的变化和意义

目的 观察比较中介素在低氧性肺动脉高压大鼠血浆和支气管肺泡灌洗液含量的变化.方法 雄性Wistar大鼠被随机分为4组,对照组、低氧1周组、2周组、3周组.利用放免分析法测定大鼠血浆和支气管肺泡灌洗液的含量.结果 低氧组大鼠血浆和支气管肺泡灌洗液中介素含量明显高于对照组.同时支气管肺泡灌洗液和血浆的变化趋势一致.结论 中介素血浆和支气管肺泡灌洗液含量增高,提示机体可能对缺氧性肺动脉高压起到一定的缓冲和保护作用.     

中介素在低氧性肺动脉高压大鼠中的变化和意义

目的 观察比较中介素在低氧性肺动脉高压大鼠血浆和支气管肺泡灌洗液含量的变化.方法 雄性Wistar大鼠被随机分为4组,对照组、低氧1周组、2周组、3周组.利用放免分析法测定大鼠血浆和支气管肺泡灌洗液的含量.结果 低氧组大鼠血浆和支气管肺泡灌洗液中介素含量明显高于对照组.同时支气管肺泡灌洗液和血浆的变化趋势一致.结论 中介素血浆和支气管肺泡灌洗液含量增高,提示机体可能对缺氧性肺动脉高压起到一定的缓冲和保护作用.     

卢帕他定干预兔油酸型急性肺损伤的研究

急性肺损伤(ALI)就是通常所定义的急性非心源性的水肿性肺损伤，是临床重症监护病人主要的死亡原因。本研究以油酸静注制备新西兰兔ALI模型，检测动脉血气参数变化，测定支气管肺泡灌洗液(BALF)中蛋白和血小板活化因子(PAF)、细胞间粘附分子-1(ICAM-1)及白细胞介素-8(IL-8)的含量，检测肺湿/干重(W/D)比值，观察组织病理学变化。结果表明，卢帕他定能抑制兔油酸型ALI的Pa_o2的下降，降低BALF中PAF，ICAM-1和IL-8的含量，减少蛋白渗出，降低肺W/D比值，减轻肺组织病理学损伤。卢帕他定可明显改善兔ALI，作用机制可能与抑制炎症因子合成与释放有关。     

大黄对肠源性感染早期肺损伤大鼠内毒素的影响

目的：观察大黄治疗大鼠肠源性肺损伤时内毒素变化。方法：采用大鼠盲肠结扎并穿孔(CLP)造成腹腔感染，每日在麻醉下经胃管灌注大黄1次。分别在术前及术后24，48，72，96，120 h处死1组大鼠，检测肺毛细血管通透性、支气管肺泡灌洗液(BALF)的中性粒细胞百分率,分析血浆、肺组织和BALF的内毒素水平。结果：肺毛细血管通透性、BALF的中性粒细胞百分率及血浆、肺组织和BALF的内毒素含量逐渐增加，时间越长作用越明显。治疗组比感染组增加较慢、幅度较小。结论：大黄可阻止肺组织的内毒素含量和中性粒细胞数量的增加，减轻肺损伤。     

隐孔菌多糖对小鼠内毒素性肺损伤的保护作用

目的研究隐孔菌多糖(cryptoporus polysaccharide,CP)对脂多糖(LPS)诱导小鼠急性肺损伤(ALI)的影响。方法LPS气管内滴入诱导小鼠ALI模型,设立对照组、模型组、隐孔菌多糖(1、10、30mg·kg-1)组和地塞米松(0·5mg·kg-1)组,检测支气管肺泡灌洗液(BALF)和肺组织中中性粒细胞的浸润情况、比色法测定伊文氏兰渗出量及BALF中的中性粒细胞髓过氧化物酶(MPO)、超氧根阴离子自由基(O2·)含量,观察肺组织病理及肺湿重/干重比值改变,ELISA法检测肺组织中TNF-α和IL-10含量。结果隐孔菌多糖(1、10、30mg·kg-1)尾静脉给药能够抑制BALF MPO活性,改善ALI小鼠BALF及肺组织中的炎症细胞的聚集和肺水肿程度,降低肺组织中TNF-α水平及升高IL-10/TNF-α比值。结论隐孔菌多糖通过抑制中性粒细胞黏附、趋化、减轻肺水肿等改善LPS诱导的小鼠ALI。     

Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.     

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist. Effects on microvascular permeability, hypotension and nephrosis.

The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.     

Edaravone, a novel antidote against lung injury and pulmonary fibrosis induced by paraquat?

Edaravone (MCI-186) is a potent free radical scavenger used clinically to treat acute brain infarction. Its antioxidant ability maybe also do favor to protect against lung injury. In this study, we evaluated whether edaravone could protect against lung injury and pulmonary fibrosis in paraquat-treated rats. Rats were divided into four groups (Control group, Edaravone group, Paraquat intoxication group and Paraquat+Edaravone group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected and analyzed biochemically and histologically. Paraquat intoxication significantly increased malondialdehyde (MDA), hydroproline, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in lung tissue and BALF, and also increased mRNA expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in lung tissue, but decreased SOD and GSH-PX activity in lung tissue and BALF. Histological examination of paraquat-treated rats showed acute injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as fibrosis. After edaravone treatment, levels of MDA, IL-6, TNF-α and hydroproline decreased, but SOD and GSH-PX activity in lung tissue and BALF increased. In addition, the mRNA expression of TGF-β1, MMP-2, and TIMP-1 down-regulated. Histological examination showed that edaravone decreased interstitial edema, inflammatory cell infiltration and prevented the process of pulmonary fibrosis.     

Inhibitory effects of cryptoporus polysaccharide on airway constriction, eosinophil release, and chemotaxis in guinea pigs

AIM: To study effects of cryptoporus polysaccharide (CP) on antigen-induced bronchoconstriction, eosinophil peroxidase (EPO) release in vivo, and on platelet activating factor (PAF)-induced eosinophil chemotaxis in vitro in guinea pig. METHODS: The asthma model of guinea pig was formed with ovalbumin (OVA). The changes of lung resistance (RL) and dynamic lung compliance (Cdyn), EPO level in bronchoalveolar lavage fluids (BALF) and eosino- phil migration were determined. RESUL…     

Endotoxin treatment protects rats against ozone-induced lung edema: with evidence for the role of manganese superoxide dismutase.

Ozone is a strong oxidizing agent that can cause lung damage and edema. There is evidence that it does so by causing peroxidation of membrane lipids. However, the elevation in lung activity of copper, zinc superoxide dismutase (Cu, ZnSOD), and manganese superoxide dismutase (MnSOD) during exposure to ozone suggests that increased production of superoxide could contribute to lung edema caused by ozone. This latter observation, and preliminary evidence that treatment of rats with endotoxin elevates lung activity of MnSOD without elevation of the activity of Cu, ZnSOD, catalase (CAT), or glutathione peroxidase (GP), led to the present study. We treated rats with endotoxin, exposed them to different concentrations of ozone, measured lung wet weight to dry weight ratio, thiobarbituric acid-reactive material (TBAR), and assayed lung tissue for Cu, ZnSOD, MnSOD, CAT, and GP activity. Our major findings are, (1) a strongly edemogenic concentration of ozone-lowered MnSOD activity; (2) endotoxin treatment of air-breathing rats did not decrease lipid peroxidation as indicated by the lung concentration of TBAR; (3) induction of increased MnSOD activity in lung by treatment with endotoxin was associated with virtually complete protection against an otherwise edemogenic concentration of ozone, with less lipid peroxidation, and with less loss of weight; and (4) this protection occurred without elevated Cu, ZnSOD, CAT, or GP activity.     

Lactoferrin protects against lipopolysaccharide-induced acute lung injury in mice

Lactoferrin (LF) plays various anti-inflammatory roles in inflammation experimentally induced by lipopolysaccharides (LPS). But the protective effects of LF on LPS-induced acute lung injury (ALI) have not been elucidated. In this study, we aimed to study the effects of LF on ALI caused by LPS in mice. At 1h before or after LPS injection, an intraperitoneal injection of LF (5mg/body) was administered. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analyses 12h after LPS exposure. We found that both prophylactic and therapeutic administration of LF significantly decreased the W/D ratio of the lung and protein concentration in the BALF. LF significantly reduced the pulmonary myeloperoxidase activity and the number of total cells in the BALF 12h after LPS challenge. LF treatment markedly attenuated lung edema, alveolar hemorrhage and inflammatory cells infiltration. Moreover, LF also decreased the production of TNF-α and increased interleukin-10 in the BALF. These results firstly indicate that LF may protect against LPS-induced ALI in mice.     

白藜芦醇苷对大鼠内毒素休克性肺损伤的保护作用

目的 :研究白藜芦醇苷 (PD)对内毒素休克大鼠肺损伤的保护作用。方法 :将大鼠随机分为单纯手术组、内毒素休克组、PD预防组和PD治疗组4组。利用静脉注射内毒素复制大鼠内毒素休克的动物模型。对各组大鼠平均动脉压 (MAP)的动态变化、肺系数、肺通透指数、肺泡灌洗液 (BALF)中蛋白含量、肺组织一氧化氮合酶 (NOS)含量等指标进行观测 ,并结合光镜下肺组织的病理变化 ,探讨PD对内毒素休克性肺损伤的保护作用。结果 :PD可不同程度地阻止内毒素引起的血压下降 ,明显降低内毒素导致的肺系数、肺通透指数、BALF中蛋白含量、NOS含量的增高 ,从而减轻内毒素导致肺组织病理损伤的程度 ,且PD预防组较PD治疗组的效果更好。结论 :PD对大鼠内毒素休克性肺损伤具有保护作用 ,且预防性用药效果更佳。